This subproject is one of many research subprojects utilizing the resources provided by a Center grant funded by NIH/NCRR. The subproject and investigator (PI) may have received primary funding from another NIH source, and thus could be represented in other CRISP entries. The institution listed is for the Center, which is not necessarily the institution for the investigator. Since neither an effective vaccine or microbicide to prevent HIV transmission exist, we are currently examining combination strategies to see synergy exists between these approaches. Initial studies using the gp41-targeted fusion inhibitor peptide T-1249 as the microbicide arm, with an rAd26 prime, rAd5HVR48 boost as the vaccine arm and SIVmac251 as the vaginal challenge virus ("high-dose", progesterone-treated macaque model) demonstrated better protection in the combination arm than vaccine or microbicide arms alone. We are currently performing a second study with additional animals to determine if different vaccines may also demonstrate protection when used in combination with a microbicide.